Collision cell multipole

ABSTRACT

Mass spectrometer collision/reaction cell multipole and method. The multipole may have first and second portions and an intermediate portion therebetween, the first and second portions operating at first and second q values lower than a third q value at the intermediate portion. A low-mass cut-off of the multipole may be controlled by varying a q value from a first to at least a second value. The multipole may have multipole electrodes disposed about a central axis and having a respective first portion, second portion, and intermediate portion therebetween which is radially closer to the central axis. This offers relatively high acceptance and ion transmission, while providing low-mass cut-off for removing undesired/interfering ions and helping reduce background count.

FIELD OF THE INVENTION

The present invention relates to a collision cell multipole in a massspectrometer and an associated method. The term “collision cell” is usedherein to mean a collision and/or reaction cell. The invention may beused with various mass spectrometry techniques, including LC-MS, GC-MS,fragmentation (MS/MS) in LC-MS² or GC-MS² environments, or as a reactioncell for any types of reaction, including collisional activation,fragmentation by ion-ion, ion-electron, ion-photon or ion-neutralinteraction, etc. The operation of the collision cell is independent ofthe nature of the ion source, which could be API (atmospheric pressureionization), such as ICP, MALDI or ESI as well as ionization in vacuum,including EI, MALDI, ICP, MIP, FAB, SIMS, but the following discussionwill focus on embodiments using inductively coupled plasma massspectrometry (ICP-MS).

BACKGROUND OF THE INVENTION

The general principles of ICP-MS are well known. ICP-MS instrumentsprovide robust and highly sensitive elemental analysis of samples, downto the part per trillion (PPT) range and beyond. Typically, the sampleis a liquid solution or suspension and is supplied by a nebuliser in theform of an aerosol in a carrier gas; generally argon or sometimeshelium. The nebulised sample passes into a plasma torch, which typicallycomprises a number of concentric tubes forming respective channels andis surrounded towards the downstream end by an helical induction coil. Aplasma gas, typically argon, flows in the outer channel and an electricdischarge is applied to it, to ionise some of the plasma gas. Aradiofrequency electric current is supplied to the torch coil and theresulting alternating magnetic field causes the free electrons to beaccelerated to bring about further ionisation of the plasma gas. Thisprocess continues until a steady plasma state is achieved, attemperatures typically between 5,000 K and 10,000 K. The carrier gas andnebulised sample flow through the central torch channel and pass intothe central region of the plasma, where the temperature is high enoughto cause atomisation and then ionisation of the sample.

The sample ions in the plasma next need to be formed into an ion beam,for ion separation and detection by the mass spectrometer, which may beprovided by a quadrupole mass analyser, a magnetic and/or electricsector analyser, a time-of-flight analyser, or an ion trap analyser,among others. This typically involves a number of stages of pressurereduction, extraction of the ions from the plasma and ion beamformation, and may include a collision/reaction cell stage for removingpotentially interfering ions.

A problem encountered with the above analysers, especially relativelylow mass resolution devices such as quadrupoles, is the presence in themass spectrum of unwanted artefact ions which interfere with thedetection of some analyte ions. The identity and proportion of artefactions depends upon the chemical composition of both the plasma supportgas and the original sample. The interfering ions are typicallyargon-based ions (such as Ar⁺, Ar₂ ⁺, ArO⁺), but may include others,such as ionised metal oxides, metal hydroxides or, depending on thematrix of the solution, molecules including matrix ions, e.g. ArCl⁺ orClO⁺ in an HCl (hydrochloric acid) solution. The collision/reaction cellis used to promote ion collisions/reactions with a gas which isintroduced into the cell, whereby the unwanted molecular ions (and Ar⁺)are preferentially neutralised and pumped away along with other neutralgas components, or dissociated into ions of lower mass-to-charge ratios(m/z) and rejected in a downstream m/z discriminating stage.

A collision cell is a substantially gas-tight enclosure through whichions are transmitted and it is positioned between the ion source and themain mass analyser. A collision/reaction target gas, such as hydrogen orhelium, among others, is supplied into the cell. The cell typicallycomprises a multipole (a quadrupole, hexapole, or octopole, forexample), which is usually operated in the radio frequency (RF)-onlymode. Generally speaking, the RF-only field does not separate masseslike an analysing quadrupole, but has the effect of focusing and guidingthe ions along the multipole axis. The ions collide and react withmolecules of the collision/reaction gas and, by various ion-moleculecollision and reaction mechanisms, interfering ions are preferentiallyconverted to non-interfering neutral species, or to other ionic specieswhich do not interfere with the analyte ions.

An additional technique for discriminating against artefact or reactionproduct ions which pass out of the collision cell is by kinetic energydiscrimination. The principle of this technique is that larger,polyatomic interfering ions will have a larger cross section forcollisions in the collision cell, so generally lose more kinetic energythan analyte ions. By running a downstream device, such as the analysingquadrupole, or merely an electrically biased aperture, at a morepositive potential than that of the collision cell, a kinetic energybarrier is provided. The more energetic analyte ions can overcome thisbarrier, while the collision cell product ions are impeded.

Some examples of collision cells using multipole rods are as follows.U.S. Pat. No. 5,767,512 relates to the selective neutralisation ofcarrier gas ions with a charge transfer gas. WO-A1-00/16375 relates tothe use of a collision cell to selectively remove unwanted artefact ionsby causing them to interact with a reagent gas. U.S. Pat. No. 6,140,638relates to the operation of the collision cell with a pass band. U.S.Pat. No. 5,847,386, U.S. Pat. No. 6,111,250, and US-A1-2010/0301210relate to the use of a DC axial field gradient on the rods in thecollision cell. U.S. Pat. No. 5,939,718 and U.S. Pat. No. 6,417,511relate to various assemblies of more than one multipole or a multipoleand a ring stack. U.S. Pat. No. 5,514,868 and U.S. Pat. No. 6,627,912relate to kinetic energy filtering methods.

In view of the above, it would be desirable to provide an alternativeand/or improved collision cell multipole which can efficiently transmitanalyte ions while reducing or preventing the passage of interferingspecies towards a downstream mass analyser. The invention aims toaddress the above and other objectives by providing an improved oralternative multipole and associated method.

SUMMARY OF THE INVENTION

According to one aspect of the invention, there is provided a collisioncell multipole, the multipole comprising a plurality of multipoleelectrodes disposed about a central axis, at least some of the multipoleelectrodes having a respective first portion, second portion, andintermediate portion therebetween, wherein the intermediate portion isradially closer to the central axis than its respective first portionand second portion.

In this way, the arrangement can provide a high acceptance at theentrance end, operation at a relatively high frequency to pass lower m/zvalue ions, and a reduced diameter region for ejecting lower m/z ionsand for removing background interfering species. However, in addition tothese advantages, providing an increased diameter region downstream ofthe narrowed region provides for improved transmission of ionsdownstream, out of the collision cell.

Embodiments of the invention can provide an RF-only multipole providedwith a changing q value along its length. Preferably, the q valuechanges from a first, relatively low value at the entrance end of themultipole to at least a second value which is relatively higher than thefirst. In this way, relatively high acceptance and ion transmission maybe achieved, while also providing low-mass cut-off for removingundesired, potentially interfering ions and helping to the reducebackground count. In a preferred embodiment, there is provided a furtherchange in q value downstream, whereby the q value changes to a third,relatively low value at the exit end of the multipole, preferably thesame as the first q value.

According to another aspect of the invention, there is provided a methodof operating a multipole in a collision cell, the multipole comprising afirst portion, a second portion and an intermediate portiontherebetween, the method comprising the step of operating the first andsecond portions at respective first and second q values lower than athird q value at the intermediate portion.

According to another aspect of the invention, there is provided a methodof operating a multipole in a collision cell, comprising controlling alow-mass cut-off of the multipole by varying a q value in the multipolefrom a first value to at least a second value.

Advantageously, the collision cell is provided as a substantiallygas-tight enclosure.

Other preferred features and advantages of the invention are set out inthe description and in the dependent claims which are appended hereto.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be put into practice in a number of ways and someembodiments will now be described by way of non-limiting example only,with reference to the following figures, in which:

FIG. 1 shows a stability diagram in a-q space;

FIG. 2 shows a plot of ion transmission in standard mode;

FIG. 3 shows a plot of ion transmission in collision mode;

FIG. 4 shows a stepped multipole according to one embodiment;

FIG. 5 shows a simulation of static potentials;

FIG. 6 shows a close-up of a portion of FIG. 5;

FIG. 7 shows simulated ion trajectories in a stepped multipole instandard mode;

FIG. 8 shows simulated ion trajectories in a stepped multipole incollision mode;

FIG. 9 shows simulated ion trajectories in a stepped multipole incollision mode;

FIG. 10 shows a sloped stepped multipole according to one embodiment;

FIG. 11 shows a sloped multipole according to one embodiment;

FIGS. 12 a-d show a radially narrowed electrode according to oneembodiment;

FIG. 13 shows a centrally stepped multipole according to one embodiment;

FIGS. 14 a-b show a curved multipole according to one embodiment;

FIG. 15 shows a plot of ion transmission for various multipoleconfigurations in standard mode;

FIG. 16 shows a plot of ion transmission for various multipoleconfigurations in collision mode;

FIG. 17 shows a plot of continuous background count for variousmultipole configurations;

FIG. 18 compares simulated ion trajectories in a curved multipole and astepped multipole;

FIG. 19 compares simulated ion trajectories in a curved multipole fordifferent m/z ions;

FIG. 20 shows a schematic stability diagram according to one embodiment;

FIG. 21 shows schematically a mass spectrometer according to oneembodiment;

FIG. 22 shows a plot of applied RF amplitude with mass of interestaccording to one embodiment; and

FIG. 23 shows schematically a mass spectrometer according to oneembodiment.

DESCRIPTION OF PREFERRED EMBODIMENTS

Quadrupoles, used as mass filters or ion guides, are commonplace in massspectrometry applications today. A general overview of this device isgiven in “The Quadrupole Mass Filter: Basic Operating Concepts”; Millerand Denton; pp. 617-622, vol. 63, no. 7, July 1986. As is known, thefiltering action of a quadrupole mass analyser is provided by theapplication of a time-varying, radio-frequency (RF) potential and astatic DC potential to the rods of the quadrupole. The same RF potentialis applied to opposing pairs of rods in the quadrupole, with the RFpotential on one pair being 180° out of phase with the RF potentialapplied to the other pair. A positive DC potential is applied to one ofthe pairs and a negative DC potential is applied to the other of thepairs. The resulting field within the quadrupole permits only selectedions to pass through it with a stable trajectory, while radiallydisplacing ions with an unstable trajectory, filtering them out of theion beam due to collisions with the electrodes.

The calculation of full solutions to the behaviour of ions in aquadrupole is complex, but it is possible to simplify matters bydefining two parameters, a and q, and plotting regions in a-q spacewhere solutions to the equations of motion of the ions are stable. Theparameters, a and q, are defined such that

$a = {{\frac{4\;{eU}}{\omega^{2}r_{0}^{2}m}\mspace{14mu}{and}\mspace{14mu} q} = \frac{2\;{eV}}{\omega^{2}r_{0}^{2}m}}$where e is the charge on the particle, U is the magnitude of the appliedDC potential, V is the magnitude of the applied RF potential, ω is theangular frequency (2 nf) of the applied RF potential, r₀ is thequadrupole field radius (the distance from the central axis of thequadrupole to each electrode of the quadrupole) and m is the mass of theion.

FIG. 1 shows an example of a stability diagram in a-q space, as shown inthe above paper. When the quadrupole is operated with the parameters aand q related linearly (i.e., so that the ratio a/q is constant, so thatthe ratio U/V is also held constant) the gradient of the line representsa mass scan line. If the mass scan line is arranged to pass over orclose to the tip of the stability graph, the particular mass-to-chargeratio passing through the tip will have a stable trajectory, while otherions will not. By increasing V and U simultaneously, while keeping theirratio constant, the magnitude of the mass represented on the mass scanline increases, so that a mass spectrum may be obtained. If the ratioU/V is lowered, the mass scan line passes through a broader region ofthe stability graph, so that the mass resolution of the quadrupole wouldbe reduced.

When such a quadrupole is operated in a collision cell, the quadrupoleis typically operated with RF-only potentials (no DC potentials), sothat it generally acts as an ion guide for the ions passing through thecollision cell. In terms of the stability diagram shown in FIG. 1, thisis equivalent to setting the parameter a to 0 (since U=0). As shown inFIG. 1, the mass scan line is represented by a line in a-q space whichhas a gradient of 0 and crosses the a axis at a=0. Thus, the quadrupoleoperates with a relatively broad stability region, so that a largeportion of the mass scan line falls within the region of stabletrajectories. As can be seen from inset B in FIG. 1, however, thequadrupole operating in RF-only mode is a high-pass mass filter,rejecting ions of m/z below a certain value. In the example shown inFIG. 1, m/z values above 15 are passed, while m/z values of 14 or lowerare unstable and are filtered out. Of course, various parameters andoperating conditions will affect the range of the high-pass filter (themass range of an ICP-MS is typically in the range of around 4 u toaround 280 u (unified atomic mass unit, sometimes referred to as Da). Asshown in FIG. 1, at values of q above approximately 0.91, ions becomeunstable in the RF-only quadrupole.

While operating a mass spectrometer with a collision cell with anRF-only quadrupole operating so as to satisfactorily transmit ions ofmedium to high mass (tens to low hundreds of u), the inventors foundthat low-mass elements such as Li were not transmitted through thecollision cell when operated in kinetic energy discrimination (KED)mode. In order to try to address this, for a given mass, the inventorssought to reduce the value of q. This was achieved by operating thequadrupole at a higher frequency, of 3 MHz, instead of 1 MHz. From thestability diagram of FIG. 1, it can be seen that, with an increasedfrequency, lower-mass ions are able to have a q value which lies withinthe stability region of the quadrupole.

In this specification, standard (STD) mode is operation of the collisioncell with no collision/reaction gas therein; i.e., in a fulltransmission mode. Collision cell technology (CCT) mode is operation ofthe collision cell with a collision/target gas therein, but no kineticenergy discrimination. Kinetic energy discrimination (KED) mode isoperation of the collision cell with a collision/target gas therein andwith the application of a kinetic energy barrier downstream of thecollision cell.

FIGS. 2 and 3 show comparisons of measurements obtained with thequadrupole in the collision cell operating at 1 MHz and at 3 MHz, withFIG. 2 representing operation of the collision cell without a target(collision or reaction) gas and FIG. 3 representing operation with sucha target gas and operation in kinetic energy discrimination mode. As canbe seen, in both cases, there was greater transmission of all analytesat 3 MHz, compared to 1 MHz. For example, for lithium, FIG. 2 shows acount rate of around 120 kcps at 1 MHz and around 185 kcps at 3 MHz;while FIG. 3 shows a zero count rate at 1 MHz and a count rate of around300 cps at 3 MHz. It can be seen, then, that increasing the frequencyallows for an increase in transmission of lower-mass ions, such as Li.

However, despite increasing the transmission of low-mass analyte ions,it was also found that background ions formed in, or at the exit of, thecollision cell undesirably passed out of the cell and downstream. Forexample, with higher frequency and the same RF amplitude, the q value islower for higher masses, so that—at different settings, optimized e.g.for the analysis of heavy metals—40Ar and other high-intensity(predominant) masses are no longer rejected by the quadrupole. It willbe understood that, on the one hand, it is desirable to be able to passlow-mass ions at all, when they are the target of analysis (this isachieved by adjusting the voltage (i.e., the RF amplitude, V)accordingly). On the other hand, it is desirable to be able to rejectrelatively low-mass interferences (especially argon), when the analysistarget has a higher mass, ranging through all heavy metals, e.g. fromiron (m/z=56) or V, Cr, Mn, to uranium (m/z 238) or even higheractinoids. Typically, downstream of the collision cell, the transmittedions are transported through an ion optical device which acts toseparate ions from neutral gas which emanates from the collision cell,such as, for example, by being accelerated into a double deflector lens,before they enter the mass analyser. In this region, disadvantageouslysome of the ions may become neutralised and make their way as fastneutrals through the mass analyser (typically a quadrupole mass filter)into the detector. This leads to a continuous background count of around5 to 10 cps in standard mode (i.e., non-CCT mode, with no target gas inthe collision cell). The background count is proportional to the totalion current transmitted through the collision cell and also proportionalto the gas pressure in the collision cell. Thus, with increasedtransmission of undesired ions such as Ar⁺, O⁺ and N⁺ there is a generalincrease in the production of fast neutrals and therefore an increase inthe background count. When operating at 1 MHz, in the originalconfiguration, this increasing background count was not present, becausethe quadrupole was operated at a q value which did not generally passsuch mass values (it is believed that the change in q caused a greatertransmission of 40Ar and other interfering species, giving rise to thiseffect).

A similar finding was made when the quadrupole of a conventionalcollision cell (with r₀=4.5 mm) was operated at a still higher frequencyof 4.5 MHz; namely, increased ion transmission, but increased backgroundcount. Thus, in an attempt to address this, a further test was conductedwith quadrupole rods operated with r₀=2 mm and V=4.5 MHz. However, inthis case it was found that the transmission of ions was reduced to 70%compared to the conventional cell. The transmission of ions at smallmasses was comparable, but a strongly negative bias voltage on thecollision cell of less than −10 V was found to be necessary.Furthermore, the sensitivity in KED mode was lower than with thestandard cell and matrix recovery (i.e., the effect on sensitivity of ananalyte ion, e.g. Co, in different concentrations of a matrix solution,e.g. a nickel solution of 100 ppm or 1000 ppm compared to a blanksolution) is also not better than with the standard collision cell. Itis understood that these effects were caused by space charge in thecollision cell.

Since operating the quadrupole at a higher frequency but with a lowerinner quadrupole radius was not successful, the inventors developed theidea of a stepped quadrupole, where the inner quadrupole radius at theentrance end is greater than an inner quadrupole radius towards thedownstream end. In this way, the inventors believed that the quadrupolecould have a high acceptance at the entrance of the collision cell(i.e., so that ions could pass into the quadrupole, with reduced orsubstantially no effect from fringing fields at the entrance end of thequadrupole), to improve ion transmission into and through thequadrupole. At the same time, to account for the increased frequency ofoperation of the quadrupole, the inventors believed that the smallerradius between the rods at the downstream end would help to removelow-mass ions formed inside the collision cell (i.e., m/z valuessignificantly lower than the m/z of current interest; usually, this willmean the removal of Ar or compounds containing Ar, N or O). The higherradius region at the entrance of the quadrupole has a lower low-mass cutoff (i.e., passes ions of a lower m/z value), but this would also meanthat low-mass ions formed inside the collision cell would betransmitted, so the lower radius region at the downstream end of thequadrupole has a higher low-mass cut off (i.e., passes ions with higherm/z values). This arrangement is generally understood to provide abroader transition region between the high-pass mass filtercharacteristic and the low-mass stop-band characteristic of thequadrupole and to provide suppression or reduction of unwanted ionsformed in the collision cell.

FIG. 4 shows schematically a collision cell 10 with an entrance aperture20 and an exit aperture 30 and comprising a quadrupole 40. The figureshows a cross-section of the cell, so that only two, opposing rods, 40a, 40 b are shown. Each rod 40 a, 40 b is stepped in the downstreamdirection and, in this case, has two steps 44, 46. A first, upstreamsection 42 of the quadrupole rod 40 a is configured at a first radialdistance r₁ from the central axis about which the quadrupole isarranged. A second section 44, downstream of the first section 42, isstepped radially towards the central axis and is configured at a radialdistance r₂ from the axis lower than r₁. A third section 46 of thequadrupole rod, downstream of the second section 44, is provided with asecond step towards the central axis and is configured at a radialdistance r₃ from the axis lower than both r₁ and r₂. In the arrangementshown in FIG. 4, r₁=4.5 mm, r₂=3.75 mm, and r₃=3.0 mm. The overall axiallength of each rod was 133 mm.

However, the presence of steps in the quadrupole leads to the creationof pseudo-potential barriers along the central axis, resulting in axialforces which can retard or even reflect ions. As a result, low-mass ionsare not transmitted through the stepped quadrupole as well as in thequadrupole with no steps.

A simulation of the static electric potential field in the quadrupole ofFIG. 4 is shown in FIG. 5, and a close-up of one of the stepped regionsis shown in FIG. 6. As can be seen, the steps in the quadrupole create arepulsive field which can reflect or slow down the ions, especiallyclose to the rods.

To investigate this further, ion trajectory simulations were performedwith a quadrupole having a single step at the downstream end, operatedwith r₁=4.5 mm, r₂=3.0 mm, V=3 MHz, and q=0.47 for the upstream part ofthe multipole. FIG. 7 shows the simulation when the collision cell isoperated in standard mode (i.e., with no target gas). As can be seen,higher m/z ions are transmitted, but low-energy ions (typically, low m/zvalue ions) are reflected at the step. FIG. 8 shows the ion trajectorysimulation when the collision cell is operated in CCT (collision celltechnology; target gas in the cell) mode. In this case, the collisioncell is supplied with helium at a pressure of 3 Pa, and a bias voltageof −21 V is applied to the collision cell. Here, it can be seen thatlithium is nearly completely rejected in the collision cell, soeffectively cannot pass out of the collision cell. FIG. 9 shows an iontrajectory simulation, also in CCT mode, but with a pressure reduced to2 Pa. As can be seen, again, ions are heavily reflected at the abruptradius change of the quadrupole, so most ions do not pass through thecollision cell.

One way considered by the inventors to address the effect of thepseudo-potential barrier resulting from the stepped quadrupole rods isto “soften” or smooth the abruptness of the change in radius, byproviding a sloped transition region between the steps, as shownschematically in FIG. 10. Here, a quadrupole rod with two steppedportions 44, 46 is provided with sloped transition regions 43, 45 intothe steps.

Taking this principle further, FIG. 11 shows a quadrupole havingquadrupole rods 60 with an axially inclined inner rod surface 62, havinga largest radius at its entrance end and a lowest radius at its exitend. With the surface 62 having a substantially constant gradient inthis way, pseudo-potential barrier reflections should be minimised or atleast reduced.

With the thickness of each rod increasing in the radial direction, atthe region or regions of reduced diameter from the central axis, in someembodiments the rods may be narrowed in the radial direction towards thecentral axis, so that there is sufficient room around the axis for eachof the multipoles. FIG. 12 shows such a tapered or narrowed electrode,suitable for use in the arrangement shown in FIG. 11. FIG. 12 a shows aplan view of a quadrupole rod 70, as would be seen from the central axis(i.e., the part of the rod 70 facing the central axis). FIG. 12 b showsa side view of the rod 70, with the rectangular cuboidal portion 72being arranged radially furthest from the central axis in use and awedge portion 74 being radially closest to the central axis. FIG. 12 cshows an elevation view from the upstream end 70 a of the rod 70 andFIG. 12 d shows an elevation view from the downstream end 70 b of therod. As can be seen, the radially inner portion 74 narrows from a firstwidth W1 to a second width W2 (less than W1) towards the downstream end,where the rod is radially closer to the central axis. This allows thefour rods of the quadrupole to be arranged symmetrically about thecentral axis with sufficient room.

One alternative to providing narrowed portions of the rods is to spacethe rods further apart where the inscribed radius within the quadrupoleis greater (i.e., at the upstream, entrance end). However, thisconfiguration has a number of disadvantages, including the possibilityof the ions being affected by the electric field from the surroundingmaterial of the collision cell.

An alternative embodiment for addressing the effect of thepseudo-potential barriers resulting from the quadrupole being steppedtowards its downstream end is shown in FIG. 13. In this embodiment, thestepped portions are configured at and about the middle of the rods. Inthis way, the arrangement can provide a high acceptance at the entranceend, operation at a relatively high frequency to pass lower m/z valueions, and a reduced diameter region for ejecting lower m/z ions and forremoving background interfering species. However, in addition to theseadvantages, providing an increased diameter region downstream of thenarrowed region provides for improved transmission of ions downstream,out of the collision cell. One contribution to this effect may be fromthe ions being accelerated by a gradient in the effective potential atthe downstream end. This may provide a (very slight) acceleration forions which are off-axis (the effective gradient is zero along therotational symmetry axis, and increases towards the rods). However,calculations show that this acceleration effect is very small, if notactually negligible. The reasons for the positive effect of this shapeare not fully understood. It is possibly due to a reduction ofRF-heating, allowing the ion trajectories to remain straighter when theypass through the downstream opening, giving lower ion losses downstreamof the collision cell. This effect is shown in FIG. 18, which isdiscussed below.

Referring to FIG. 13, there is shown schematically a collision cell 10with an entrance aperture 20 and an exit aperture 30 and comprising aquadrupole 80. The figure shows a cross section of the cell, so thatonly two, opposing rods 80 a, 80 b are shown. Each rod 80 a, 80 bcomprises a number of steps extending in a radial direction towards thecentral axis of the quadrupole. In this case, there are five steps 82-90symmetrically arranged about the (longitudinal) centre of thequadrupole, with the central step 86 being radially closer to thecentral axis than its adjacent steps 84, 88, which are themselvesradially closer to the central axis than the outermost steps 82, 90 ofthe quadrupole. To put it another way, the first step 82, at theupstream end of the quadrupole, is configured at a first radial distancer₁ from the central axis; the second step 84, adjacent and downstream ofthe first step 82, is configured at a second radial distance r₂ from thecentral axis; the third step 86, adjacent and downstream of the secondstep 84, is configured at a radial distance r₃ from the central axis;the fourth step 88, adjacent and downstream of the third step 86, isconfigured at a radial distance r₄ from the central axis; and the fifthstep 90, adjacent and downstream of the fourth step 88, is configured ata radial distance r₅ from the central axis. r₃ is the shortest distance,while r₁ and r₅ are the longest distances. In the embodiment shown inFIG. 13, r₁=r₅=4.5 mm; r₂=r₄=3.75 mm; and r₃=3.0 mm. The overall lengthof each quadrupole rod in the axial direction is 133 mm. The RFamplitude V is preferably 400 V. As is known, the RF amplitude may beadjusted in dependence on the m/z of interest, as shown by way ofexample in the plots in FIG. 22. Here, the three different plotsrepresent the variation in RF amplitude V with changing m/z of interestfor (1) operation in standard mode, (2) operation in CCT mode, and (3)operation in KED mode. For plots (1) and (2), the voltage amplituderises quickly with mass, giving a low-mass cut-off relatively close to(but below) the target mass, until a maximum amplitude is reached,generally corresponding to a low-mass cut-off which rejects undesiredmasses (40Ar, in particular), while allowing transmission of a range ofhigher masses. Embodiments may therefore be configured to operate inthis way: to keep the low-mass cut-off following close to the targetmass over a first mass range (e.g., up to approximately m/z=80), then toprovide a relatively stable, flat (or only slowly increasing) low-masscut-off over a second, higher mass range. This can be advantageous inrejecting low-mass interferences and not requiring switching of the RFamplitude when cycling through high masses.

FIG. 14 shows a further embodiment in which the inner multipole radiusnarrows from the entrance end of the multipole to its centre and thenwidens again to its downstream, exit end. In this embodiment, the changein radius is provided by a curved surface of each electrode. Modellinghas shown that the stepped portions of the previous embodiment tend toreflect or retard more ions with low energy than multipole electrodeswith smoothly curving shapes. FIG. 14 a shows a plan view of theelectrode 100; i.e., as would be seen from the central axis. FIG. 14 bshows a side view of the electrode 100, from which it can be seen thatthe electrode 100 comprises a generally rectangular cuboidal portion 102and a convexly curved portion 104, disposed radially more closely to thecentral axis of the multipole in use. In the embodiment of FIG. 14, thecurved portion 104 also narrows or tapers in the direction of thecentral axis, to allow the rods to be accommodated about the axis inuse. In some embodiments, it may not be necessary to narrow or taper thecurved portion in this way. Furthermore, while it can be seen that inthe embodiment of FIG. 14 the curved portion 104 does not extend fullyto the ends of the generally rectangular cuboidal portion 102, in otherembodiments the curved portion may extend along the full length of theelectrode 100. Of course, it will be appreciated that the electrodes aretypically positioned and held in place by insulating rod holders at eachend, so providing a non-curved portion towards each end of the rods mayfacilitate engagement in such holders.

It should be noted that the curved electrodes 100 are, depending on themethod, generally easier to manufacture than the stepped electrodes ofthe previous embodiment. Typical materials for the electrodes are(stainless) steel and sometimes molybdenum or titanium, but manymaterials may be used, including carbon or coated glass. Many ways ofholding multipoles together are known, including gluing, clamping orbolting to various types of holders, or directly into an enclosure(which is usually present to establish a zone of increased gas pressureor to confine a collision/reaction gas that is different from thesurrounding gas, e.g., H, He, NH₃, N₂, etc.). Manufacturing methodsinclude milling, grinding, erosion, casting, polishing or combinationsthereof, and many others. Currently, the preferred method is for theelectrodes to be ground to the desired shape, so it is advantageous tohave shapes conforming to combinations and sections of various boxes,cones, cylinders, spheres, etc.

In the embodiment shown in FIG. 14, the electrodes 100 are arrangedabout the central axis such that the upstream end and the downstream endof each rod is at a radial distance of 4.5 mm from the central axis andthe centre of each rod (i.e., the closest part of the curved portion 104to the central axis) is configured at a radial distance of 3.0 mm fromthe central axis. The radius from the centre of the curved portionvaries smoothly towards the outer radius of 4.5 mm. The overall lengthof the electrode 100 is 133 mm in the preferred embodiment. Of course,it will be understood that, in other embodiments, different values forthese parameters may be used and different curvatures of the curvedportion may be selected. Selection of these variables may be made andoptimised with the help of ion trajectory simulations, as will bereadily appreciated.

FIGS. 15 and 16 show comparisons of ion transmission through thecollision cell using a) a quadrupole with straight rods, b) a quadrupolewith five steps (as shown in FIG. 13), and c) a quadrupole with curvedelectrodes (as shown in FIG. 14). In FIG. 15, the collision cell wasoperated in standard mode (i.e., with no target gas added), while inFIG. 16, the collision cell was operated with a target gas of helium ata pressure of 2.5 Pa, in KED mode. As can be seen, for all analyte ions,in both standard mode and CCT mode, the ion transmission is better withthe curved electrodes compared with the stepped electrodes. Indeed, thetransmission for the curved quadrupole is comparable to the transmissionfor straight rods in all modes (it is noted that the ion transmissionfor Li in KED mode is, however, somewhat lower), but is also able toprovide good background reduction at the same time. Thus, by moving theradially narrowed region of the quadrupole to the centre of thecollision cell, it is possible to improve the transmission of Li and theoverall transmission as well.

FIG. 17 shows measurement data and a plot of the continuous backgroundcount measured for different m/z values for quadrupoles having a)straight rods set at 4.5 mm from the central axis, b) rods with asingle, downstream step, taking the radius from 4.5 mm to 3 mm, c) rodswith two, downstream steps, taking the radius from 4.5 mm to 3.75 mm andthen to 3 mm, and d) curved rods, with the radius varying from 4.5 mm atthe entrance end to 3 mm in the centre, back to 4.5 mm at the exit end.As can be seen, the background count with straight rods operated at thehigher frequency of 3 MHz led to background count rates of 6 or morecps. The provision of the steps or curved portion in the electrode rodssignificantly reduced the background count, generally to around 1 orless per second. Thus it can be seen that applying a higher frequency RFvoltage to the electrodes and narrowing the internal radius of theelectrodes at and about the centre of the multipole provides improvedion transmission through the multipole, while reducing the backgroundcount.

In the table below, measurements of the lithium count at the detectorwhen the collision cell was operated in KED mode are shown for a numberof different configurational and operational set-ups. As can be seen,the conventional straight-rod quadrupole with r₀=4.5 mm, operated at 1MHz, shows a zero count rate for lithium (for a Li concentration insolution of 1 ppb). Increasing the frequency to 3 MHz led to asignificant increase in the lithium detection, with a count rate of 400cps. Maintaining this higher frequency, but reducing r₀ to 3 mm, led toa drop in the detection of lithium to 50 cps. Providing 1, 2 or 4 steps,as discussed above, led to count rates of 35 cps, 80 cps, and 70 cps,respectively. However, with the embodiment using curved rods, varyingfrom 4.5 mm to 3 mm at the centre, and back to 4.5 mm at the downstreamend, the lithium count rate was significantly higher, at 250 cps. Thusit can be seen that, with embodiments of the invention, not only can iontransmission generally be improved and background counts be generallyreduced, but specifically lithium transmission can be improved.

Cell geometry Li [cps] straight 4.5 mm 1 MHz 0 straight 4.5 mm 3 MHz 400straight 3 mm 3 MHz 50 1 step 4.5-3 mm 3 MHz 35 2 steps 4.5-3.75-3 mm 3MHz 80 4 steps 4.5-3.75-3-3.75-4.5 mm 3 MHz 70 curved 4.5-3-4.5 mm 3 MHz250

Li Transmission in KED Mode

FIG. 18 shows ion trajectory simulations a) through a collision cellwith a curved quadrupole with the smallest radius in the middle, and b)through a collision cell with a stepped quadrupole with the smallestradius at the downstream, exit end. In both cases, the collision cellswere operated in KED mode, with a He collision gas at a pressure of 2.5Pa, a potential of −60 V at the entrance to the collision cell, acollision cell bias of −21 V, and q=0.3 for the radius at the entranceto the quadrupole. The ions had a m/z of 75 and are shown travellingfrom right to left in the simulation. As can be seen, the multipolewhich has the narrower exit radius gives rise to a wider distributionangle of ions travelling downstream. The multipole with the largerradial distance—or, to put it another way, with a reduced q value for agiven mass—at its exit end results in a lower angular and energy spread(smaller phase space) of the emerging ion beam. This effect may be dueto a reduced effect of fringing fields at the downstream end, and/orreduced RF heating, as discussed above. This is beneficial infacilitating the downstream extraction and/or guiding of the ion beamfrom the collision cell, towards the mass analyser.

FIG. 19 shows mass discrimination ion trajectory simulations through acollision cell with a curved quadrupole with the smallest radius in themiddle, for a) m/z of 75, and b) m/z of 40. In both cases, the collisioncell was operated in standard mode (i.e., with no collision gassupplied), with a potential of −20 V at the entrance to the collisioncell, a collision cell bias of −5 V, a particle initial energy E₀ of 5eV, and q=0.3 for the radius at the entrance to the quadrupole. The ionsare shown travelling from right to left in the simulation. As can beseen, the ions at m/z=75 are transmitted through the collision cell,while the ions at m/z=40 are discriminated against and rejected withinthe quadrupole in the collision cell. Thus, embodiments with curvedmultipole rods may be used to provide the high-pass (low-mass cut-off)characteristics associated with RF-only quadrupoles, to removeundesired, lower mass ions.

As will be appreciated, embodiments with a curved electrode shapeoperated in RF-only mode give rise to a variable stability parameter qalong the central axis for a given mass. FIG. 20 shows a schematicstability diagram for the curved quadrupole embodiment. Since a=0 forRF-only operation of the quadrupole, the q axis has an exemplary massscale shown along it. In this example, the RF peak amplitude is constantand configured to transmit m/z=100. As can be seen, a first stabilityplot is given for r₀=4.5 mm and a second, smaller stability plot isgiven for r₀=3.0 mm. In operation, the upper boundary of stabilityremains constant at q=0.905, but this boundary moves along the massscale with axial distance through the curved quadrupole. At the entranceto the curved quadrupole, the boundary is given by the first stabilityplot for r₀=4.5 mm. With further penetration into the quadrupole towardsits centre, the stability plot shrinks on the mass scale—so the boundarymoves—to the second stability plot for r₀=3.0 mm. Upon passing thecentre of the quadrupole and passing further downstream towards its end,the stability plot expands again on the mass scale—so the boundary againmoves—back to the first stability plot for r₀=4.5 mm. In thisembodiment, ions of m/z below 33 are unstable everywhere. Ions of m/zbelow 75 are stable at the entrance but become unstable in the centre,so, for example, 40Ar is rejected in the collision cell.

Another way of describing this example is to say that, for a given mass,the q value starts at a relatively low value at the entrance to thequadrupole and grows by a factor of 2.25 towards the centre[q₂/q₁=(4.5)²/(3.0)²] and then shrinks again to its initial lower valuetowards the downstream end.

FIG. 21 shows schematically an embodiment of the invention in which anICP mass spectrometer incorporates a collision cell with the curvedquadrupole described above. A sample 110, typically a liquid solution orsuspension, is supplied by a nebuliser 120 in the form of an aerosol ina carrier gas; generally argon or sometimes helium. The nebulised samplepasses into a plasma torch 130, which is arranged to form a plasma froma plasma gas, typically argon. The carrier gas and nebulised sample flowthrough a central channel of the torch and pass into the plasma, wherethe temperature is high enough to cause atomisation and then ionisationof the sample. The sample ions in the plasma are sampled and skimmedinto a reduced-pressure ambient and subjected to ion-extraction optics140, to form an ion beam. There are typically further stages of pressurereduction towards the mass analyser, and ion focusing, guiding and/ordeflection optics 150 may also be provided to direct the ion beamtowards the analyser. A collision/reaction cell 160 is provided upstreamof the mass analyser. The collision cell 160 is provided with a curvedquadrupole as described in the above embodiments and especially as shownin FIG. 14. Ions transmitted through the collision cell 160 pass into anelectrostatic double deflection lens (or dog-leg lens) 170, which isused to deflect ions away from the axis coming from the collision celland onto the axis of the mass analyser 180. Neutral species and photonsare not affected by the field of the double-deflector lens 170, so aregenerally prevented from entering the mass analyser 180 and causinginterference with measurements. The mass analyser 180 is a quadrupolemass filter in this embodiment and its rods are operated with both a DCpotential and an RF potential, so that it acts as a bandpass mass filterto selectively pass ions with a desired m/z value on to a detector 190.The detector 190 may be an electron multiplier, a microchannel plate, ora Faraday cup, among others. Of course, the mass spectrometer mayalternatively be provided by a magnetic and/or electric sector analyser,a time-of-flight analyser, or an ion trap analyser, FT/MS, among others.

Referring to the collision cell 160 in more detail, there is typicallyprovided a focusing lens (such as a tube lens) in front of the cell. Inother embodiments, there may be provided a further mass discriminationmeans upstream of the collision cell. This may be especially so when thecollision cell is used for fragmentation of molecular parent ions intofragment daughter ions, as typically performed in life sciences massspectrometry, to select a particular parent ion of interest to enter thecollision cell.

The collision cell comprises a housing with a gas inlet for supplyingone or more target gases to the cell. The housing itself, or insulatingelectrode holders disposed within the housing, may be used to hold theelectrode rods precisely in position. The entrance aperture to thecollision cell is provided by a diaphragm with an orifice therethroughand acts as an entrance lens, to which a DC potential is typicallyapplied. The exit aperture to the collision cell is provided by anotherdiaphragm with an orifice therethrough and acts as an exit lens, towhich another DC potential is typically applied.

The electrodes are arranged to provide a quadrupole and each of the fourrods is configured according to one of the embodiments described herein.One preferred configuration for the quadrupole electrodes is to providethem with flat surfaces in cross-sections normal to the central axis ofthe quadrupole. Such electrodes are called “flatapoles” and can beuseful in reducing noding due to higher order components of the electricfield (in an ideal quadrupole, the oscillation of the ions along theaxis has a fixed period, somewhat like standing waves on a string. Thefirst “node” of this oscillation is at the entrance opening. Then thedeviation of the ions from the central axis increases and decreasesperiodically with distance from the entrance opening. Unlike with astring, the position of the exit diaphragm does not influence theposition of the nodes, but they depend only on the applied RF potential,velocity and mass of the ions, etc. It can be understood that, when anode happens to lie at the exit diaphragm, ion transmission may be verygood, and, when an antinode happens to be at the exit opening,transmission may be substantially worse). Such flat surfaces can be usedin any of the above embodiments.

One particularly preferred configuration of the electrodes is as above,with each electrode having a curved (convex) shape extending radiallytowards the central axis and being centred along the axial length of theelectrode. In this arrangement, a cross-sectional configuration of thequadrupole normal to the central axis has each electrode at a respectiveedge of a square centred on the central axis. The electrodes remain atthe edges of such a square along the length of the quadrupole, with thesize of the square varying along the length and being smallest in themiddle of the quadrupole. That is, the rod-to-rod distance at both endsof the quadrupole is larger than the rod-to-rod distance at the centre.

The quadrupole electrodes are provided with a voltage supply (not shown)which is configured to supply RF-only voltages to opposite pairs ofelectrodes, the RF voltages applied to one pair of electrodes being 180°out of phase with that applied to the other pair. The RF voltage supplyis configured to supply a desired RF frequency, which may be in therange from 200 KHz to 20 MHz, preferably in a range from 1, but mostpreferably 3 to 6 MHz. The most preferred frequency is 4 MHz. Foroctopoles, the frequency is preferably about twice the value/range asfor quadrupoles. For other purposes and MS/MS applications, a preferredrange is 0.5 MHz to 5 MHz. The optimum frequency depends on the targetmass, the multipole dimensions and the multipole order, as will beappreciated.

The voltage supply may be configured to maintain such frequencyconstantly. In some embodiments, the multipole electrodes may beconfigured, for example, having no electrically resistive layer providedthereon, so the RF voltage supply may supply a respective RF voltage toeach electrode, wherein for each respective electrode the same amplitudeis applied to substantially the whole of the electrode (i.e., there isno voltage drop across an individual electrode). The same, or anadditional, voltage supply may be used to provide a bias DC voltage toall of the electrodes, for controlling the axial potential in thecollision cell and/or to provide variable DC voltages to the focusing,entrance and/or exit lenses.

FIG. 23 shows schematically a mass spectrometer according to a furtherembodiment of the invention. Like parts are labelled with the samereference numbers as in FIG. 21. This figure is shown principally to setout the preferred DC bias potentials applied to the various componentsof the collision cell 160. As can be seen, the bias potentials for thecollision cell are provided for a) standard (STD) mode; i.e., with nocollision gas, in pass-through or transmission mode; b) collision celltechnology (CCT) mode; i.e., with collision/reaction gas added to thecollision cell; and c) kinetic energy discrimination (KED) mode; i.e.,with a retarding potential barrier applied to prevent low-energy ionsfrom passing on to the mass analyser. It will be appreciated that thevalues used are typically selected (or automatically tuned) to providefavourable ion lenses within their operating environment.

It will be appreciated that the above embodiments provide an RF-onlymultipole (i.e., not operating in mass-resolving mode where DCpotentials of opposite polarities are applied to different pairs ofopposing electrodes; either no DC potential or the same (magnitude andpolarity) DC potential may be applied to all electrodes equally,however, since this has a biasing effect, not a mass-resolving effect).The RF-only multipole is provided with a changing q value along itslength. The q value changes from a first, relatively low value at theentrance end of the multipole to at least a second value which isrelatively higher than the first. In this way, relatively highacceptance and ion transmission may be achieved, while also providinglow-mass cut-off for removing undesired, potentially interfering ionsand helping to the reduce background count. In a preferred embodiment,there is provided a further change in q value downstream, whereby the qvalue changes to a third, relatively low value at the exit end of themultipole, preferably the same as the first q value.

The change in q value in the above embodiments is achieved by changingthe radial distance of the electrodes from the central axis, in astep-wise or curved manner. In other embodiments, as an alternative orin addition to the change in radius, the change in q value may beeffected by changing the frequency of the RF potential applied todifferent portions of the electrodes in the longitudinal/axialdirection—i.e., by providing a relatively high frequency at the upstreamend of the multipole and changing this to a relatively lower frequencydownstream thereof. If the q value is to be reduced again towards thedownstream end, the frequency would be increased again at the downstreamend to a third frequency, preferably the same as the first. This may beeffected by providing two or three or more electrically segmentedelectrodes (isolated from one another), with respective connections to aRF voltage supply arranged to provide the same RF amplitude but atdifferent frequencies. Alternatively, the multipole may be subjected todirect drive of the multipole with fast electronic switches; or a squareor triangular wave (possibly amplified by a (resonant) coil transformerin the usual way) could be used, directing the ground and “overtone”(i.e. harmonics) frequencies to the different parts of the multipolewith a crossover (similar to an audio crossover, just at higherfrequencies).

In still other embodiments, as an alternative or in addition to thechange in radius and/or frequency, the change in q value may be effectedby changing the peak magnitude of the RF potential applied to differentportions of the electrodes in the longitudinal/axial direction. At theupstream end of the multipole, a first, relatively low RF magnitude isapplied, then a second, relatively higher RF magnitude is applied to adownstream portion. If the q value is to be reduced again towards thedownstream end, the RF amplitude would be reduced again at thedownstream end to a third RF amplitude, preferably the same as thefirst. This may be effected by providing two or three or moreelectrically segmented electrodes (isolated from one another), withrespective connections to a RF voltage supply arranged to provide thesame RF frequency but at different amplitudes. Alternatively, eachelectrode may be provided with a resistive coating with two or moreconnections to a RF voltage supply arranged to provide the same RFfrequency but at different amplitudes to the connections. For example,with an arrangement where the q value changes from low to high and backto low again along the length of the multipole, the resistively coatedelectrodes may be provided with three connections to the RF voltagesupply; one at either end and one in the middle. The upstream anddownstream ends would be configured with a relatively low RF amplitude,preferably the same, and the central connection would be configured witha relatively higher RF amplitude.

Alternatively still, instead of a multipole as described above, astacked ring ion guide could be employed, as shown inUS-A1-2010/0090104. In this way, relative potential field amplitudes maybe achieved by changing the stacking distance, as will be understood.

As discussed above, a DC potential of the same magnitude and polaritymay be applied to each of the electrodes of the multipole, so as tocreate a DC axial field gradient along the multipole in the collisioncell, to drive ions through it. This is especially advantageous athigher collision cell pressures. From life sciences mass spectrometry,it is known that the optimum gradient is a function of (e.g.,approximately or low multiples of) kT/L (with k being the Boltzmannconstant, T being the temperature, and L being the mean free path forthe ions).

While the above embodiments have described RF-only modes of operation,in some embodiments, the multipole may be run in a mass-resolving mode.That is, DC potentials of the same magnitude but opposite polarity maybe applied to different pairs of opposing electrodes, to provide amass-discriminating effect in the multipole.

While the above discussion has focused on quadrupoles, embodiments ofthe invention my employ a hexapole, octopole, or other multipole devicein the collision cell, with the principles of the above discussionrelating to quadrupoles being correspondingly applied. Quadrupoles arein general preferred, for their low-mass cut-off effect to rejectunwanted ions in the collision cell to reduce molecular ion formationand for their better collisional focusing in the CCT mode.

The multipole electrodes of the above embodiments may be flatapoles ormay be rods of generally circular, hyperbolic, square, rectangular orother polygonal cross-section; they may be flat or plate-likeelectrodes; or they may be of various other shapes and configurations,as will be understood from the above discussion.

Embodiments of the invention make use of one or more of the propertiesof a relatively large multipole internal diameter—giving rise to a highacceptance of ions at the entrance to improve ion transmission into themultipole; a relatively high frequency of the RF voltage applied to themultipole electrodes—giving rise to a lower low-mass cut-off to allowlow-m/z analyte ions to pass into the collision cell; a relativelysmaller multipole internal diameter downstream of the entrance—givingrise to the rejection of low-m/z ions which may be formed in thecollision cell and a reduction in the background count caused byneutrals from a high ion current; and a relatively larger multipoleinternal diameter downstream of the reduced-diameter region—giving riseto a smaller angular and energy spread of those ions out of thecollision cell for improved downstream processing.

Although preferred embodiments have the smallest radial region of themultipole symmetrically disposed at the centre of the multipole, thesmallest radial region may be configured off-centre, so that themultipole is not symmetrical. In this way, the acceptance at theentrance and the reduced angular and energy spread at the exit may beoptimised by adjustment of the position along the length of themultipole where the reduced radius portion is provided. Indeed, thecurved or stepped shape of the reduced radius portion need not itself besymmetrical, but may have some degree of skewness in form.

Furthermore, while the above embodiments have described the electrodesof the multipole as each having the same shape, this need not be so inall embodiments. It may be desirable in some applications to arrange asingle opposing pair of electrodes (or more than one respective opposingpair in higher multipoles) to have a respective reduced radius region,while providing the remaining opposing pair (or pairs in highermultipoles, or even individual electrodes in odd-numbered multipoles)with different respective forms. In particular, it may be desirable toprovide the electrodes disposed in the X-direction with different shapesfrom the electrodes disposed in the Y-direction.

Other variations, modifications and embodiments will be apparent to theskilled person and are intended to form part of the invention.

The invention claimed is:
 1. A method of operating a multipole in acollision cell, the multipole comprising a first portion, a secondportion and an intermediate portion therebetween, the method comprisingthe step of operating the first and second portions at respective firstand second q values lower than a third q value at the intermediateportion; wherein the step of operating the first and second portions atrespective first and second q values lower than the third q value at theintermediate portion comprises at least one of: positioning theintermediate portion radially closer to a central axis of the multipolethan the first portion and the second portion; or applying a differentRF voltage amplitude to the intermediate portion relative to the RFvoltage amplitude applied to the first portion and the second portion;or applying a different RF voltage frequency to the intermediate portionrelative to the RF voltage frequency applied to the first portion andthe second portion.
 2. The method of claim 1, further comprisingreceiving ions into the first portion of the multipole, transmitting atleast some of the received ions through the intermediate portion with arelatively smaller inner multipole radius, and passing at least some ofthe transmitted ions out of the second portion.
 3. The method of claim1, further comprising applying a respective RF voltage to each electrodeof the multipole at a frequency in the range from 3 MHz to 6 MHz.
 4. Themethod of claim 1, further comprising providing a supply of a target gasto the collision cell to a pressure in the range from 0.01 Pa to 1000Pa.
 5. The method of claim 1, further comprising the step of applying anaxial DC field gradient to the multipole.
 6. The method of claim 1,further comprising the step of tracking a low-mass cut-off of themultipole close to a changing target mass over a first mass range, thenmaintaining the low-mass cut-off relatively stable over a second, highermass range.
 7. The method of claim 1, wherein the multipole comprises aplurality of multipole electrodes, and wherein at least some of themultipole electrodes comprise one or more respective pairs of radiallyopposing electrodes in the multipole.
 8. The method of claim 1, whereinthe multipole comprises a plurality of multipole electrodes arrangedaround the central axis, and wherein the at least some of the electrodesare stepped in a direction of the central axis.
 9. The method of claim8, wherein a respective transition to or from the or each step issloped.
 10. The method of claim 1, wherein the multipole comprises aplurality of electrodes arranged around the central axis, and whereinthe at least some of the electrodes are curved in a direction of thecentral axis.
 11. The method of claim 1, wherein the multipole comprisesa plurality of electrodes arranged around the central axis, and whereina cross-section normal to the central axis of a surface of eachelectrode radially closest to the central axis is substantially flat.12. The method of claim 1, wherein the multipole is a quadrupole.